Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Classic human enteric caliciviruses (HuCVs) have a distinctive morphology and are primarily associated with pediatric acute gastroenteritis. Although morphologically distinct from the small round structured viruses (SRSVs), the classic HuCVs are thought to be closely related and were anticipated to have a similar genome organisation. We report the first genome sequence and molecular characterisation of a classic human enteric calicivirus associated with a case of acute vomiting and diarrhoea in an infant. The RNA genome (7266 nt) is smaller than the genome of SRSVs from the two genetic groups and has a unique arrangement of open reading frames. Further analysis of the 3' terminal 3 kb from a second unrelated isolate confirmed this genomic organisation. Analysis of capsid and RNA polymerase sequences together with the unique genomic organisation of classic HuCV suggest these viruses are more closely related to the animal caliciviruses than the enteric SRSV group of viruses.
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PMID:Human enteric caliciviruses have a unique genome structure and are distinct from the Norwalk-like viruses. 766 89

Two outbreaks of gastroenteritis in the UK which occurred nine days apart at Lymington and Southampton hospitals were investigated. The clinical and epidemiological features of both outbreaks were characteristic of small round-structured virus (SRSV) infection with rapid onset of diarrhoea and/or nausea and vomiting and propagation of the outbreaks by secondary spread. SRSV particles were observed by immune electron microscopy (EM) in 60% of faecal samples from both outbreaks and no other pathogens were detected. The index case for the second outbreak was a patient who was admitted with diarrhoea and vomiting after being discharged from Lymington hospital during the first outbreak. The possibility that the two outbreaks were caused by the same strain of SRSV was investigated by the polymerase chain reaction (PCR). New inosine-containing PCR primers were designed to amplify the RNA polymerase region of SRSV cDNA from genetic groups I and II. The PCR using the group II primers achieved a higher detection rate for SRSVs in faecal samples (68% of samples positive from both outbreaks) than immune EM. SRSVs were not detected using the group I primers or using conventional degenerate PCR primers. The nucleotide sequences of PCR amplicons from both outbreaks were identical providing molecular epidemiological evidence for the involvement of a single SRSV strain. Comparison of the RNA polymerase region of this virus with the equivalent regions of genetic group I (69.4-75.0% amino acid identify) and genetic group II (88.9-100% amino acid and 77.1-88.1% nucleotide identity) SRSVs revealed that the causative SRSV was a distinct member of genetic group II.
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PMID:Polymerase chain reaction detection of small round-structured viruses from two related hospital outbreaks of gastroenteritis using inosine-containing primers. 777 39

We retrospectively investigated the clinical and histopathologic features of hospitalized patients infected with human immunodeficiency virus who had symptomatic lactic acidosis syndrome at a university teaching hospital during 1995-2000. Twelve patients were identified, 11 during 1998-2000; of these, 5 died with rapid progression to otherwise unexplained multiple-organ failure. All had extensive prior exposure to nucleoside analog reverse-transcriptase inhibitors (NRTIs). At presentation, the most commonly identified NRTI component of antiretroviral regimens was stavudine plus didanosine. Eleven patients presented with abdominal pain, nausea, and/or emesis. Eight patients had prior acute weight loss (mean [+/-SD], 12+/-5.3 kg). Median venous plasma lactate levels were > or =2-fold greater than the upper limit of normal (2.1 mmol/L). Serum transaminase levels were near normal limits at presentation. Histopathologic studies confirmed hepatic macrovesicular and microvesicular steatosis in 6 patients. Concurrent chemical pancreatitis was identified in 6 patients. The increasing number of cases identified during the study period suggests that physicians better recognize symptomatic lactic acidosis and/or that cumulative NRTI exposure may increase the risk for this syndrome.
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PMID:Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: a report of 12 cases. 1169 4

In the Netherlands about 4 million people (283/1000) suffer from gastroenteritis every year, of which 500,000 cases are caused by 'Norwalk-like viruses' (NLVs), formerly known as 'small round-structured viruses'. The reports of two outbreaks illustrate the difficulties in determining the cause and source of the infection. The course is usually mild, but complications may be serious and ought to be documented. Vomiting and diarrhoea are the prominent signs and dehydration is the most common complication. Strict hygiene is warranted to prevent spreading of the disease. NLVs are highly infectious, notably via the faecal-oral route or by aerosols generated by vomiting. Fecally contaminated seafood and other food components that are not heated are an important source of infection, the main vehicle being sewage water. The microbiological quality control of food is often still based on bacteriological contamination, and therefore viral contamination may remain unnoticed. Reverse transcriptase PCR is a recent diagnostic tool.
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PMID:[Outbreaks of viral gastroenteritis, in particular due to the Norwalk virus: an underestimated problem]. 1281 28

Tipranavir (TPV) is a non-peptidic protease inhibitor belonging to the class of 4-hydroxy-5,6-dihydro-2-pyrones, which exhibits potent and specific activity against HIV type I (HIV-1) and 2 (HIV-2). Clinically effective plasma levels of TPV are achieved by concomitant administration of ritonavir (RTV). Therefore, TPV has been coadministered with RTV in clinical trials. TPV has demonstrated antiviral activity against HIV-1 isolates that are resistant to reverse-transcriptase and selected peptidic protease inhibitors. Therefore, TPV is emerging as one of the newer drugs in the armamentarium against HIV-1 in patients demonstrating multi-drug resistance. TPV administered orally to humans exhibits linear pharmacokinetics at doses of 100 - 2000 mg. Steady-state plasma levels are attained within 7 days of initiating multiple dosing. The half-life of the drug is approximately 6 h at steady-state. The plasma concentration is lower with repeated dosing than predicted from single-dose studies due to induction of the cytochrome p450 3A4 isoform of the liver microsomal enzyme system. Phase II clinical trials have shown that the administration of TPV and RTV in combination is safe and generally well-tolerated in HIV-1-infected adults. Phase III trials are underway to compare the efficacy of this drug versus other antiretroviral regimens. Gastrointestinal toxicity has been described with TPV, the most frequently reported side effects being diarrhoea, nausea, vomiting and abdominal pain. There is no known evidence of teratogenicity or effect on fertility. TPV dosed twice-daily, in the range of 500 - 1250 mg and combined with 100 - 200 mg of RTV has been shown to substantially and durably reduce viral load in HIV-1-infected drug-naive and experienced patients.
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PMID:Tipranavir: a novel non-peptidic protease inhibitor for the treatment of HIV infection. 1458 57

Nucleoside reverse-transcriptase inhibitors (NRTIs) have been associated with functional and structural mitochondrial abnormalities, leading to several adverse events, such as increased serum lactic acid levels and lactic acidosis. Mild-to-moderate, asymptomatic hyperlactataemia has been frequently reported in human immunodeficiency virus (HIV)-infected patients treated with NRTIs, with an estimated prevalence between 15% and 35%. On the contrary, symptomatic, severe hyperlactataemia and lactic acidosis are less common, with an incidence ranging from 1.7 to 25.2 cases per 1000 person-years of antiretroviral treatment, and are associated with a remarkable mortality rate, which varies from 30% to 60% in different studies. The clinical presentation of lactic acid syndrome is non-specific and includes asthenia, malaise, nausea, vomiting, abdominal pain, weight loss, tachypnoea, dyspnoea, liver steatosis and increased transaminase levels, and risk factors include previous or concurrent therapy with stavudine or didanosine. Management of symptomatic lactic acid alterations involves NRTI-therapy interruption and supportive care, while natural history of hyperlactataemia is still unknown, and it is uncertain whether asymptomatic patients with increased lactate concentrations are at increased risk of developing lactic acidosis.
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PMID:Hyperlactataemia and lactic acidosis in HIV-infected patients receiving antiretroviral therapy. 1568 Oct 97

A 21-year-old soldier developed anorexia, vomiting, diarrhea and fever 10 days after returning to the United States from an 8-month deployment in Afghanistan. His symptoms persisted over the next 5 days until he presented in respiratory failure with a partial pressure oxygen: concentration of inspired oxygen (PaO(2):FiO(2)) ratio of 63, requiring urgent intubation and ventilator support. Chest roentgenogram revealed diffuse bilateral alveolar opacities consistent with acute respiratory distress syndrome. Although sputum and blood cultures did not reveal a causative agent, Giemsa-stained blood smears were positive for Plasmodium vivax alone, which was later confirmed by small subunit ribosomal RNA polymerase chain reaction amplification. After a tenuous course marked by splenic rupture and prolonged requirement for ventilator support, the patient ultimately recovered. Although generally considered benign, this and other recent reports of vivax malaria-associated lung injury emphasize the need for persistent pursuit of the diagnosis in febrile travelers returning from vivax endemic locations as well as aggressive monitoring for and management of life-threatening complications.
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PMID:Plasmodium vivax-associated acute respiratory distress syndrome after extended travel in Afghanistan. 1787 Jun 35

Norovirus outbreaks occur worldwide every year and have become more frequent over the last few years. There were extensive outbreaks in Hong Kong from May to July 2006 and our aim was to describe nosocomial outbreaks from 1 May 2006 to 31 July 2006 in this retrospective observational study. A total of 38 confirmed norovirus outbreaks involving 218 patients were identified. Most of these patients were elderly with a mean age of 74.5 years (range: 3 months to 97 years); 62% of them were either totally or partially dependent for help with daily activities, 83.9% had underlying chronic medical problems and 56% had limited mobility. In all, 97.2% of individuals presented with diarrhoea and only 46.3% of them had vomiting. The median duration for diarrhoea was 3 days and the longest 24 days. The median duration of vomiting was one day and the longest 15 days. Fever occurred in one-third of all cases. Reverse transcriptase-polymerase chain reaction was positive for norovirus in 72.6% cases. We conclude that nosocomial norovirus infection often involves frail elderly patients with limited mobility and that these patients may have more prolonged symptoms.
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PMID:Clinical characteristics of nosocomial norovirus outbreaks in Hong Kong. 1846 26

The study was conducted to investigate the molecular epidemiology of noroviruses (NoVs) from western India. A total of 830 fecal specimens were collected during July 2005-June 2007 from children, < or =7 years of age suffering from acute gastroenteritis in Pune, Nagpur, and Aurangabad cities. All the specimens were subjected to RT-PCR, sequencing and phylogenetic analysis for detection and characterization of Genogroup I (GI) and GII NoVs. NoV positivity varied between 6.3% and 12.6% in different cities with the predominance of GII (96.6%). NoV infections were very common in the patients < or =2 years of age. A majority (55%) of the patients suffered from severe disease, however, vomiting was not experienced in 35%. Coinfections with rotaviruses were found in 10% cases. Summer month seasonality supported NoV infections in western India. The phylogenetic analysis of partial RNA polymerase and VP1 (capsid) genes identified 2 GI (GI. 2 and GI.6) and 5 GII (GII.4, GII.6, GII.7, GII.8, and GII.14) genetic clusters with possible occurrence of "2007 new-variant" of GII.4. Six different combinations of RdRp and capsid genes (GII.b/GII.3, GII.b/GII.4, GII.d/GII.3, GII.b/GII.18, GII.1/GII.12 and GII.3/GII.13) were also identified. GII.4 (52%) prevailed in 2005-2006 while the predominance of probable recombinant NoV strains (58%) was noted in 2006-2007 with the contribution of GII.b/GII.3 at 79% level. GII.b/GII.18 type identified in 37% infections in 2005-2006 was completely replaced by GII.b/GII.3 type in 2006-2007. This is the first report that highlights the norovirus epidemiology and strain diversity demonstrating possible circulation of new variants in patients with acute gastroenteritis from western India.
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PMID:Epidemiological, clinical, and molecular features of norovirus infections in western India. 1931 38

Cyclins and cyclin-dependent kinases (CDK) form a key part of the regulatory proteins that govern the cell cycle. Aberrancy in their function can lead to uncontrolled growth and proliferation of the cells which forms the basis of many human diseases, especially cancers. Seliciclib (CYC202, R-roscovitine) is a second-generation CDK inhibitor that competes for ATP binding sites on these kinases, reducing tumor growth and inducing cell death. It is a direct inhibitor of cyclin E/CDK2 and also has inhibitory effects on cyclin H/CDK7 and cyclin T/CDK9. Seliciclib leads to growth arrest and apoptosis of cell lines through activation of the p53 gene, inhibition of RNA processing and blockage of the RNA polymerase II-dependent transcription, and reduction of anti-apoptotic proteins. Seliciclib has good oral bioavailability, although its absorption is slowed by food. It is distributed rapidly to the body tissues and metabolized rapidly to a carboxylated derivative that is excreted by the kidneys. The major adverse effects of seliciclib are electrolyte disturbances (hypokalemia, hyponatremia), gastrointestinal side effects (nausea, emesis, anorexia), fatigue, transient hyperglycemia, elevation of liver enzymes and reversible elevation of serum creatinine. At present, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.
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PMID:Seliciclib in malignancies. 1993 6


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